Leptin promotes mesenchymal cells of the hematopoietic microenvironment to differentiate to osteoblasts

Abstract

Multipotential mesenchymal stromal cells (MMSCs) serve as a common precursor to osteoblasts and adipocytes. During aging, osteoblasts decrease and bone marrow (BM) fat increases, thereby converting the BM from red to yellow. Alcohol hastens this process of conversion and likely contributes to osteoporosis, anemia, aplasias and other hematopoietic deficiencies of aging. Leptin, a hormone secreted by adipocytes, increases bone density and mass, including in alcoholics. However, information on role of leptin in hematopoiesis is limited. This study was aimed at determining whether leptin affects MMSCs and opposes the effects of ethanol. Varied concentrations (10,000, 1,000, 100 and 10 pg) of leptin were added to MMSC cultures containing growth supporting medium or osteoblast‐stimulating medium. Controls were grown in medium without leptin. At various time points (days 3, 6&10), MMSC survival and proliferation was measured by alamar blue and BrdU assays, respectively. Osteoblast differentiation was quantified by alkaline phosphatase assay. Results demonstrated that leptin induced differentiation of MMSCs into osteoblasts, but did not have significant effects on MMSC survival and proliferation. We have previously demonstrated that ethanol induced proliferation and adipocytic differentiation of MMSCs. Since osteoblasts are the critical cells of the hematopoietic microenvironment, leptin may oppose adipose‐inducing effects and inhibit hematopoietic deficiencies associated with alcohol. (Supported by NIA grant AG024912)